Expression Of E-cad Research Articles

IGF-1/IGF-1R blockade ameliorates diabetic kidney disease through normalizing Snail1 expression in a mouse model.

This study investigated the role of insulin-like growth factor-1/insulin-like growth factor-1 receptor (IGF-1/IGF-1R) in the genesis and progression of diabetic kidney disease (DKD) in a streptozotocin (STZ)-induced mouse diabetes model. We showed elevated IGF-1 expression in the DKD kidneys after 16 wk of diabetic onset. Intraperitoneal administration of IGF-1R inhibitor (glycogen synthase kinase-3β, GSK4529) from week 8 to week 16 postdiabetes induction ameliorated urinary albumin excretion and kidney histological changes due to diabetes, including amelioration of glomerulomegaly, inflammatory infiltration, and tubulointerstitial fibrosis. The GSK4529 treatment also attenuated alterations in renal tubular expression of E-cad and matrix protein fibronectin. Moreover, renal fibrosis in DKD (without treatment) was associated with Snail1 overexpression that was effectively prevented by IGF-1R inhibition. Further experiments in cultured renal epithelial cells (NRK) showed that IGF-1 silencing reproduced in vivo effects of IGF-1R inhibition with markedly attenuated Snail1 expression and near normalization of the Ecad1 and fibronectin expression pattern. Further Snail1 silencing prevented high-glucose-induced changes without affecting IGF-1 expression, consistent with Snail1 acting downstream to IGF-1. The antifibrotic effects were also shown with benazepril or insulin treatment but to a much lesser degree. In summary, in STZ-induced diabetic mice, activation of IGF-1 in diabetic kidneys induces fibrogenesis through Snail1 upregulation. The diabetes-related histological and functional changes, as well as fibrogenesis, can be attenuated by IGF-1/IGF-1R inhibition.

A novel role of kynureninase in the growth control of breast cancer cells and its relationships with breast cancer.

Breast cancer is the most common malignancy among women worldwide. Kynureninase (KYNU) located in 2q22.2, which was associated with tryptophan utilization and metabolic diseases including cardiac, renal and limb defects syndrome 2. However, the role of KYNU in breast cancer (BC) development remains unclear. The expression of KYNU was examined by immunohistochemistry (IHC) in 137 primary BC tissues, and the correlation of KYNU expression with clinical pathological characteristics and the biomarkers (ER, PR, HER2, E‐cad and Ki‐67) was analysed. The role of KYNU in cancer cell proliferation, tumour growth and development was evaluated by MTT assay, soft agar colony formation assay and xenograft mouse models. Among 137 primary BC tissues, 46.7% (64/137) had high KYNU expression (IHC scores >4) while 53.3% (73/137) had low KYNU expression (IHC scores ≤4). The expression of KYNU was positively correlated with the expressions of ER (P = .002), PR (P = .007) and E‐cad (P = .03), while negatively associated with tumour grade (P = .008), tumour stage (P < .001) and the expressions of HER2 (P = .04) and Ki‐67 (P = .019). Overexpression of KYNU significantly inhibited cell proliferation in cell culture, colony formation in soft agar and xenograft BC development in NOD/SCID mice. Kynureninase suppresses BC cell proliferation, tumour growth and development. Kynureninase may function as a tumour suppressor in BC.

High Concentrations of Serum Soluble E-Cadherin in Patients With Q Fever.

Cadherins switching is a hallmark of neoplasic processes. The E-cadherin (E-cad) subtype is one of the surface molecules regulating cell-to-cell adhesion. After its cleavage by sheddases, a soluble fragment (sE-cad) is released that has been identified as a pro-carcinogenic inflammatory signal in several bacteria-induced cancers. Recently we reported that Q fever, a disease due to Coxiella burnetii infection, can be complicated by occurrence of non-Hodgkin lymphoma (NHL). Therefore, we studied E-cad switching in Q fever. The sE-cad levels were found increased in the sera of acute and persistent Q fever patients, whereas they remained at the baseline in controls groups of healthy donors, people cured of Q fever, patients suffering from unrelated inflammatory diseases, and past Q fever patients who developed NHL. These results indicate that sE-cad can be considered as a new biomarker of C. burnetii infection rather than a marker of NHL-associated to Q fever. We wondered if changes in sE-cad reflected variations in the CDH1 gene transcription. The expression of E-cad mRNA and its intracellular ligand β-catenin was down-regulated in peripheral blood mononuclear cells (PBMCs) of patients with either acute or persistent forms of Q fever. Indeed, a lower cell-surface expression of E-cad was measured in a minority (<5%) subpopulation of HLADR+/CD16+ monocytes from patients with acute Q fever. However, a very strong increase in E-cad expression was observed on more than 30% of the HLADR+/CD16+ monocytes of persistent Q fever patients, a cell subpopulation known to be a target for C. burnetii in humans. An experimental in vitro infection of healthy donors' PBMCs with C. burnetii, was performed to directly evaluate the link between C. burnetii interaction with PBMCs and their E-cad expression. A significant increase in the percentage of HLADR+/CD16+ monocytes expressing E-cad was measured after PBMCs had been incubated for 8 h with C. burnetii Nine Mile strain. Altogether, these data demonstrate that C. burnetii severely impairs the E-cad expression in circulating cells of Q fever patients.

CLINICO-PATHOLOGICAL SIGNIfiCANCE OF B-CATENIN AND E-CADHERIN EXPRESSION IN SALIVARY GLAND TUMOR AT UCH IBADAN

Objectives β-catenin (B-Cat) is a cell adhesion molecule associated with the invasion and metastasis of carcinomas of the head and neck, esophagus while reduced expression of E-cadherin (E-cad), a transmembrane glycoprotein, is associated with loss of differentiation, acquisition of an invasive phenotype, and an unfavorable prognosis in carcinomas from several sites. B-Cat & E-Cad complex are involved in cell adhesion, signal transduction & motility. Aim is to identify the clinical / pathological significance of B-Cat & E-Cad expressions in salivary gland tumors (SGTs) presenting at the University College Hospital, Ibadan. Findings The expressions of β-cat & E-Cad were analyzed in 46 SGTs (10 pleomorphic adenomas PSA, 3 basal cell adenoma, 12 adenoid cystic carcinoma ADCC, 10 mucoepidermoid carcinoma MEC, 5 acinic cell carcinoma ACC, 4 polymorphous low grade adenocarcinoma PLGA & 2 papillary cystadenocarcinoma PCADCA) by immunohistochemistry in formalin-fixed, paraffin embedded specimens (Rabbit monoclonal; Satacruz biotechnology). Result shows immunostaining of B-cat & E-Cad were membranous & cytoplasmic without nuclear involvement, staining was more severe in the ductal areas especially in PSA, there was significant loss of membranous stain in ACC on multivariate analysis. E-Cad staining loss was significantly associated with tumour stage in ACC & MEC. Conclusion loss of β-catenin adhesion molecule may be involved in the development of ACC. E-cad expression is an independent indicator of clinical aggressiveness in patients with ACC.& MEC.

SYNCHRONOUS EXPRESSION OF E-CADHERIN AND SYNDECAN-1 IN AMELOBLASTOMA: A PRELIMINARY STUDY

Objectives This study aimed to evaluate the percentage of expression and the possibility of synchronicity between E-cadherin (Ecad) and Epithelial syndecan-1 (Syn-1E) in Unicystic ameloblastoma (UAM) and solid multicystic ameloblastoma (SMA) and the association between this synchronicity and stromal immunoexpression of Syn1 (Syn1S). Findings Immunohistochemical analysis of Ecad and Syn1 was performed for 30 (15 UAM, 15 SMA) cases of ameloblastoma, the percentage of expression was evaluated with the average value for expression, and intensity was evaluated with the Immunomebrane plug-in. (Image J, BioMediTech, Finland) The percentage expression of Ecad and Syn1E was high in UAM. (p 0.05) Conclusions We observed synchronicity in the expression of Ecad and Syn1E in both types of ameloblastomas. The adhesiveness of the tumoral cells is probably related to the regulation of expression of both proteins; thus, an increase or reduction of synchronicity is related to cell invasion and the capacity to migration to the stroma, which was reflected in the behavior of the ameloblastomas in the present cases. This assumption may be further supported by an increase in expression of Syn1S in the SMAs; therefore, it is possible that the low synchronicity between Ecad and Syn1E constitute an important factor for the aggressiveness of ameloblastomas.

Cell Counts, rather than Proportion, of CD8/PD-1 Tumor-Infiltrating Lymphocytes in a Tumor Microenvironment Associated with Pathological Characteristics of Chinese Invasive Ductal Breast Cancer.

Objective This study is aimed at investigating the association of exhausted CD8+ tumor-infiltrating lymphocytes with clinic-pathological factors. Methods 133 patients diagnosed with primary invasive ductal breast cancer were recruited into the cross-sectional study consecutively. Immunohistochemistry was used to detect biomarker expression on formalin-fixed and paraffin-embedded sections. Double staining of CD8 and PD-1 was conducted on lymphocytes. Results The proportion of CD8+/PD-1− TILs was 16% among patients with axillary lymph node metastasis, significantly lower than those without metastasis (24%). The expression of CK7, CK20, or Ki-67 was not related with the proportion of phenotypes of CD8/PD-1 TILs. Younger patients had more cell counts of CD8+/PD-1− TILs than elderly patients (18/HPF vs. 9/HPF, p < 0.05). Patients with axillary lymph node metastasis had less CD8+/PD-1− TILs than those without metastasis (11/HPF vs. 27/HPF, p < 0.05). Median counts of CD8+/PD-1− TILs among patients with CK20 and E-Cad expression were 33/HPF and 14/HPF, significantly higher than those among patients with negative CK20 (16/HPF) and E-Cad expression (6/HPF). Ki-67 index had a significant correlation with cell counts of CD8+/PD-1+ TILs and CD8+/PD-1− TILs, and the correlation coefficients were 0.19 and 0.21 (p < 0.05), respectively. Conclusion The proportion of CD8+/PD-1− TILs was related with metastatic status of the axillary lymph node but cell counts of CD8+/PD-1− TILs were related with metastatic status of the axillary lymph node and expression of CK7, CK20, E-Cad, and Ki-67. Absolute cell counts, not proportion of CD8/PD-1 TILs, were more likely to distinguish clinic and pathologic characteristics of breast cancer.

Inhibition of miR-9-5p suppresses prostate cancer progress by targeting StarD13

BackgroundThis study aims to investigate the effects of inhibiting microRNA-9-5p (miR-9-5p) on the expression of StAR-related lipid transfer domain containing 13 (StarD13) and the progress of prostate cancer.MethodsThe mRNA expression levels of miR-9-5p and StarD13 were determined in several prostate cancer cell lines. We chose DU145 and PC-3 cells for further research. The CCK8 assay was used to measure the cell viability. The cell invasion and wound-healing assays were respectively applied to evaluate invasion and migration. The expression of E-cadherin (E-cad), N-cadherin (N-cad) and vimentin were measured via western blot. DU145 and PC-3 cells overexpressing StarD13 were generated to investigate the variation in proliferation, invasion and migration. A luciferase reporter assay was used to identify the target of miR-9-5p.ResultsOur results show that miR-9-5p was highly expressed and StarD13 was suppressed in prostate cancer cells. MiR-9-5p inhibition repressed the cells’ viability, invasion and migration. It also increased the expression of E-cad and decreased that of N-cad and vimentin. StarD13 overexpression gave the same results as silencing of miR-9-5p: suppression of cell proliferation, invasion and migration. The bioinformatics analysis predicted StarD13 as a target gene of miR-9-5p. Quantitative RT-PCR, western blot analysis and the dual-luciferase reporter assay were employed to confirm the prediction.ConclusionOur results show that miR-9-5p plays a powerful role in the growth, invasion, migration and epithelial–mesenchymal transition (EMT) of prostate cancer cells by regulating StarD13. A therapeutic agent inhibiting miR-9-5p could act as a tumor suppressor for prostate cancer.

High Expression B3GAT3 Is Related with Poor Prognosis of Liver Cancer.

Liver cancer is one of the most malignant tumors with poor prognosis. Finding molecular markers that can predict prognosis is very important for the treatment of liver cancer. The present research is trying to find a new biomarker for human liver cancer. The analysis of abnormal expression genes and prognosis value on liver cancer by Gene Expression Profiling Interactive Analysis (GEPIA) database, the Pathology Atlas of the Human Protein Atlas (HPA), and Kaplan Meier-plotter (KM plotter), proved that B3GAT3 might be one of the important candidates. Furthermore, we investigated the specific role of B3GAT3 on liver cancer through the transfection of B3GAT3 siRNA in HepG2 cells. The proliferation was detected using CCK8, and migration and invasion were determined using Transwell assay. Our results proved that knockdown of B3GAT3 inhibited the proliferation, migration, and invasion. Moreover, B3GAT3 knockdown inhibited the expression of EMT related proteins, N-cad, Snail, and Twist, while promoting the expression of E-cad, suggesting that B3GAT3 knockdown reversed the EMT process of liver cancer cells. In conclusion, overexpressed B3GAT3 promotes the process of tumor EMT, which is an independent prognostic marker to predict the prognosis of liver cancer and might be a potential new target for liver cancer therapy.

Assessment of epithelial-mesenchymal transition signatures in oral submucous fibrosis.

Background:Recently, the concept of field cancerization has questioned the accuracy of biopsy site selection clinically. Oral submucous fibrosis (OSMF) has a global malignant transformation rate of 7.6% despite having less dysplastic changes clinically or histologically. Hence, this study was undertaken to evaluate the expression of vimentin, epithelial-cadherin (E-Cad) and collagen IV in OSMF, using immunohistochemistry and polymerase chain reaction (PCR).Materials and Methods:One hundred and eighty- five patients with OSMF (61), with habits and no OSMF (61) and patients without habit and OSMF (63) were subjected to biopsy for sample collection. The samples were analyzed immunohistochemically for vimentin, E-Cad and collagen IV. The PCR values for vimentin and E-Cad were also done.Results:Vimentin expression was increased in OSMF patients, whereas E-Cad expression was decreased in OSMF patients.Conclusion:Epithelial–mesenchymal transition signatures are definitely positive in OSMF cases.

"Hairiness" is a Facsimile of Reorganized Cytoskeletons: A Cytopathic Effect of Coxiella burnetii.

In 1993, I reported that Coxiella burnetii transforms human B cells into hairy cells (cbHCs), the first hairy cell reported outside of hairy cell leukemia (HCL). Over last few decades, advances in molecular biology have provided evidence supporting that C. burnetii induces hairiness and inhibits the apoptosis of host cells. The present review summarizes new information in support of cbHC. C. burnetii was shown to induce reorganization of the cytoskeleton and to inhibit apoptosis in host cells. Peritoneal B1a cells were found to be permissive for virulent C. burnetii Nine Mile phase I (NMI) strains in mice. C. burnetii severely impaired E-cad expression in circulating cells of Q fever patients. B-cell non-Hodgkin lymphoma was linked to C. burnetii. Mutation of BRAF V600E was pronounced in HCL, but “hairiness” was not linked to the mutation. Risk factors shared among coxiellosis and HCL in humans and animals were reported in patients with Q-fever. Accordingly, I propose that C. burnetii induces reorganization of the cytoskeleton and inhibits apoptosis as cytopathic effects that are not target cell specific. The observed hairiness in cbHC appears to be a fixed image of dynamic nature, and hairy cells in HCL are distinct among lymphoid cells in circulation. As the cytoskeleton plays key roles in maintaining cell structural integrity in health and disease, the pathophysiology of similar cytopathic effects should be addressed in other diseases, such as myopathies, B-cell dyscrasias, and autoimmune syndromes.

MDA-19 suppresses progression of melanoma via inhibiting the PI3K/Akt pathway

ObjectiveTo investigate the effect of MDA-19 on progression of melanoma, and explore the relevant mechanism.MethodsThe melanoma cell lines, M14 and UACC257, were treated with different concentrations of MDA-19, then CCK8, clone formation assay, Transwell and flow cytometry assays were performed to examine cell proliferation, migration, invasion and apoptosis, respectively. The expression of apoptosis-related proteins (Bcl-2, Bax and caspase 3 P17), EMT and signaling pathway-related proteins were also detected by Western blot.ResultsMDA-19 inhibited melanoma cells in a dose-dependent manner. Compared to the NC group, MDA-19 significantly inhibited cell growth capacity, migration and invasion of M14 and UACC257 cells, and accelerated cell apoptosis in a mitochondrial pathway through regulating Bcl-2/Bax and Caspase 3 in M14 and UACC257 cells. Moreover, MDA-19 was observed to up-regulate the expression of E-cad and down-regulate the expression of N-cad, Vimentin and Slug in melanoma cells in vitro. Furthermore, MDA-19 could inhibit the PI3K/Akt pathway by blocking Akt phosphorylation (p-Akt) and downstream proteins, P70 and Cyclin D1 in M14 and UACC257 cells.ConclusionOur data demonstrate that MDA-19 could inhibit progression of melanoma by suppressing the PI3K/Akt pathway, suggesting that MDA-19 is a potential anti-cancer agent for therapy of melanoma.

Overexpression of CD300A inhibits progression of NSCLC through downregulating Wnt/β-catenin pathway.

BackgroundCD300A, a type I transmembrane glycoprotein receptor, plays an important role in immune response. Recent studies have reported that CD300A is involved in the development of hematological malignancies.PurposeThe objective of this study was to investigate the role of CD300A in the progression of non-small-cell lung cancer (NSCLC) and explore the associated mechanism.Materials and methodsGene Expression Profiling Interactive Analysis (GEPIA) was used to analyze the expression of CD300A in NSCLC and its prognostic value. NSCLC cell lines A549 and H1650 were transfected with siRNA-CD300A or pcDNA3.1-CD300A vector to down- or up-regulate the expression of CD300A. Cell Counting Kit 8, colony formation and Transwell assays were used to assess the effects of CD300A on cell proliferation and migration capacities. Flow cytometry was performed to examine rate of apoptosis, and the protein levels of associated proteins was detected using Western blot assay.ResultsFrom GEPIA analysis, we observed that expression of CD300A mRNA was downregulated in NSCLC and positively correlated with the overall survival of NSCLC patients. Overexpression of CD300A significantly suppressed cell growth and migration capacities of A549 and H1650 cells and induced cell apoptosis via regulating apoptosis-related proteins. Moreover, decreasing level of CD300A promoted cell growth and migration and blocked apoptosis of NSCLC cells. Furthermore, upregulation of CD300A led to significant decrease in expression level of Wnt3 and β-catenin, the pivotal components in Wnt/β-catenin signaling pathway, and an increase in expression of E-cad, a key protein in tumor metastasis, in A549 and H1650 cells; while depletion of CD300A up-regulated the Wnt/β-catenin signaling pathway. In conclusion, the present study highlighted an anti-oncogenic role of CD300A in the progression of NSCLC via inhibiting Wnt/β-catenin pathway, suggesting that CD300A might be a potential target for the treatment of NSCLCConclusionCD300A plays an anti-oncogenic role in the progression of NSCLC through inhibiting the Wnt/β-catenin pathway, suggesting that CD300A might be a potential target for the treatment of NSCLC.

GRP78 modulates cell adhesion markers in prostate Cancer and multiple myeloma cell lines

BackgroundGlucose regulated protein 78 (GRP78) is a resident chaperone of the endoplasmic reticulum and a master regulator of the unfolded protein response under physiological and pathological cell stress conditions. GRP78 is overexpressed in many cancers, regulating a variety of signaling pathways associated with tumor initiation, proliferation, adhesion and invasion which contributes to metastatic spread. GRP78 can also regulate cell survival and apoptotic pathways to alter responsiveness to anticancer drugs. Tumors that reside in or metastasize to the bone and bone marrow (BM) space can develop pro-survival signals through their direct adhesive interactions with stromal elements of this niche thereby resisting the cytotoxic effects of drug treatment. In this study, we report a direct correlation between GRP78 and the adhesion molecule N-cadherin (N-cad), known to play a critical role in the adhesive interactions of multiple myeloma and metastatic prostate cancer with the bone microenvironment.MethodsN-cad expression levels (transcription and protein) were evaluated upon siRNA mediated silencing of GRP78 in the MM.1S multiple myeloma and the PC3 metastatic prostate cancer cell lines. Furthermore, we evaluated the effects of GRP78 knockdown (KD) on epithelial-mesenchymal (EMT) transition markers, morphological changes and adhesion of PC3 cells.ResultsGRP78 KD led to concomitant downregulation of N-cad in both tumors types. In PC3 cells, GRP78 KD significantly decreased E-cadherin (E-cad) expression likely associated with the induction in TGF-β1 expression. Furthermore, GRP78 KD also triggered drastic changes in PC3 cells morphology and decreased their adhesion to osteoblasts (OSB) dependent, in part, to the reduced N-cad expression.ConclusionThis work implicates GRP78 as a modulator of cell adhesion markers in MM and PCa. Our results may have clinical implications underscoring GRP78 as a potential therapeutic target to reduce the adhesive nature of metastatic tumors to the bone niche.

Semaphorin-5A maintains epithelial phenotype of malignant pancreatic cancer cells

BackgroundPancreatic cancer (PC) is a highly aggressive disease, and the lethality of this disease stems from early metastatic dissemination where surgical removal cannot provide a cure. Improvement of the therapeutic outcome and overall survival of PC patients requires to understand the fundamental processes that lead to metastasis such as the gain of cellular migration ability. One such family of proteins, which are essential players of cellular migration, is Semaphorin. Previously, we have identified one of the Semaphorin family member, Semaphorin-5A (SEMA5A) to be involved in organ-specific homing during PC metastasis. We have also demonstrated that SEMA5A has a constitutive expression in PC cell lines derived from metastatic sites in comparison with low endogenous expression in the primary tumor-derived cell line. In this study, we examined whether constitutive SEMA5A expression in metastatic PC cells regulates tumor growth and metastatic potential.MethodsWe generated SEMA5A knockdown in T3M-4 and CD18/HPAF cells and assessed their phenotypes on in vitro motility, tumor growth, and metastatic progression.ResultsIn contrary to our initial expectations, orthotopic injection of SEMA5A knockdown cells into nude mice resulted in a significant increase in both tumor burden and liver metastases in comparison with the Control cells. Similarly, we observed higher in vitro migratory potential with pronounced morphological changes associated with epithelial-mesenchymal transition (EMT), a decrease in the expression of epithelial marker E-cadherin (E-Cad), increase in the expression of mesenchymal markers N-cadherin (N-Cad) and Snail and the activation of the Wnt-signaling pathway in SEMA5A knockdown cells. Furthermore, re-establishing SEMA5A expression with a knockdown resistant mouse Sema5A in SEMA5A knockdown cells resulted in a reversion to the epithelial state (mesenchymal-epithelial transition; MET), as indicated by the rescue of E-Cad expression and a decrease in N-Cad and Snail expression.ConclusionsCollectively, our data suggest that SEMA5A expression maintains epithelial phenotype in the metastatic microenvironment.

Clinical significance of Stathmin1 expression and epithelial-mesenchymal transition in curatively resected gastric cancer.

In our previous study, it was demonstrated that the Stathmin1 (STMN1) is overexpressed in gastric cancer (GC) and that its high expression level is associated with tumor invasion and metastasis. Epithelial-mesenchymal transition (EMT) has also been shown to be critically involved in GC invasion and metastasis. Certain studies have indicated that STMN1 may serve an important role in the EMT process. However, the association between STMN1 expression and EMT-associated markers, as well as clinicopathological characteristics of patients with GC, remains unclear. The aim of the present study was to investigate the clinicopathological significance and prognostic value of STMN1 and EMT-associated markers in GC. The expression of STMN1 and the EMT-associated proteins E-cadherin (E-Cad) and vimentin (VIM) were analyzed by immunohistochemistry in GC and adjacent non-tumorous tissues. Associations between the expression of these markers and clinicopathological parameters were analyzed. The association between STMN1 expression and EMT-associated markers was investigated in the GC cell lines BGC-803 and SGC-7901. The results revealed that STMN1 was expressed in 63.5% of the 167 GC tissues, which was significantly higher than the percentage observed in the adjacent non-tumorous tissues (P=0.003). The STMN1 expression was demonstrated to be positively associated with the VIM levels (P=0.001) and negatively associated with the E-Cad levels (P=0.022) in GC tissues. The STMN1 expression was associated with Lauren's Classification, invasion depth, lymph node metastasis and pathological Tumor-Node-Metastasis (pTNM) stage (P<0.05). In the univariate analyses, the high E-Cad expression was a positive prognostic indicator for overall survival, whereas the high STMN1 and VIM expression was a negative indicator. COX multiple regression analysis demonstrated that the pTNM stage [hazard ratio (HR) 1.912, 95% confidence interval (CI): 1.282–2.851, P=0.001] and E-Cad expression (HR 0.403, 95% CI: 0.249–0.650, P=0.000) were independent prognostic factors. It was also revealed that the expression level of E-Cad decreased, while the expression level of VIM increased by depleting STMN1 levels in GC cells. The present results suggest that the aberrant expression of STMN1 may promote tumor progression through EMT in GC.

Potential clinically useful prognostic biomarkers in triple-negative breast cancer: preliminary results of a retrospective analysis

BackgroundTriple-negative breast cancer (TNBC) has a poor prognosis, even in its early stages. In the absence of postoperative targeted treatments, intensive adjuvant chemotherapy regimens are proposed. For those favorable histologies, such as apocrine and adenoid cystic carcinoma, which frequently belong to TNBC, aggressive treatments are unnecessary.Patients and methodsWe retrospectively analyzed 631 cases of breast cancer, primary operated curatively, and followed up at our institution for at least 36 months to identify the bio-markers assessable by immunohistochemistry, to be proposed as prognostic score for tailoring adjuvant treatment to TNBC patients.ResultsThe triple-negative phenotype was found in 85 patients (13.5%). Over a mean followup of 55.7 months, relapses occurred in 106 patients (16.8%), of which 18 (2.8%) were TNBC. Recurrence was directly correlated with Ki67 and cytokeratin 5/6 (CK5/6) immunoreactivity in all breast cancer patients (P=0.005), but only marginally with CK5/6 and epithelial cadherin (E-cad) expression in TNBC patients (P=0.07). Mean event-free survival (EFS) in TNBC patients was 85.52 months compared with 100.4 months in non-TNBC patients (P=0.228). The EFS of CK5/6-negative triple-negative patients was 68.84 months compared with 98.84 months in those who were CK5/6 positive (HR =5.08; P=0.038). EFS differed among patients identified as double-positive for E-cad and CK5/6 (83.87 months), those expressing E-cad or CK5/6 (64.23 months), and those negative for both biomarkers (39.64 months).ConclusionThese preliminary results suggest that CK5/6 and E-cad are possible core biomarkers for a cost-effective prognostic evaluation of primary operable TNBC patients.

MiR-134 targets PDCD7 to reduce E-cadherin expression and enhance oral cancer progression.

Oral squamous cell carcinoma (OSCC) is a common malignancy worldwide. This study clarified the oncogenic role of miR-134 in OSCC. Reporter assays, using both wild-type and mutant constructs, confirmed that Programmed Cell Death 7 (PDCD7) gene was a potential target of miR-134. The OSCC cells exogenously expressed miR-134 exhibited reduced PDCD7 expression. As expected, exogenous miRZip-134 expression increased PDCD7 expression in the OSCC cells; additionally, PDCD7 expression suppressed the oncogenicity of the OSCC cells. By contrast, PDCD7 knockout through gene editing increased in vitro oncogenicity and neck nodal metastasis in mice, and reduced E-cadherin (E-cad) expression. PDCD7 transactivated E-cad expression via the GC-box in the promoter. Moreover, miR-134-associated cellular transformation and E-cad downregulation was attenuated by PDCD7. Downregulation of both PDCD7 and E-cad and high levels miR-134 expression was observed in OSCC tumor tissues. Activation of the miR-134-PDCD7-E-cad pathogenesis cascade occurred early during the human and murine oral carcinogenesis process. In conclusion, the oncogenic effect of miR-134 in oral carcinoma is mediated by reducing PDCD7 and E-cad expression.

LINC00657 promotes the development of colon cancer by activating PI3K/AKT pathway.

The aim of this study was to explore whether LINC00657 can regulate cell proliferation and invasion by regulating the PI3K/AKT pathway and thus participate in the occurrence of colon cancer. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was applied to detect the expression levels of LINC00657 and E-cad in colon cancer tissues and corresponding adjacent tissues obtained from 80 patients, and the correlation was analyzed between LINC00657 expression and clinical information of patients such as prognosis, tumor size, tumor stage, and distant metastasis. The expression of LINC00657 and E-cad in colon cancer cell lines was also examined, and the effect of LINC00657 on tumor cell proliferation was evaluated by cell counting kit-8 (CCK-8) assay and colony formation experiments. Meanwhile, transwell assay was performed to evaluate the influence of LINC00657 and CAPN7 on cell invasive ability. In addition, the effect of LINC00657 on CAPN7 and PI3K/AKT pathway was detected by Western blot assay. The expression levels of LINC00657 and E-cad in tumor tissues decreased remarkably, especially in patients who occurred distant metastasis. Compared with patients with highly-expressed LINC00657, the patients with lower level of LINC00657 had a worse prognosis and an advanced tumor size and TNM stage. Similarly, LINC00657 and E-cad also showed a decrease in colon cancer cell lines. After overexpression of LINC00657, cell viability and invasive ability decreased remarkably while cell apoptosis rate increased significantly. In addition, high expression of LINC00657 in an in vitro model significantly promoted CAPN7 expression and inhibited activation of PI3K/AKT pathway. LINC00657 had a low expression in colon cancer tissues, which could accelerate cell proliferation and invasion by activating PI3K/AKT pathway and inhibiting CAPN7 expression.

Clinical study on expressions of transcription factor Snail and its related proteins in non-small cell lung cancer

Objective To detect the expressions of transcription factor Snail, E-cadherin (E-cad) and N-cadherin (N-cad) in non-small cell lung cancer (NSCLC), and explore their correlations. Methods The expression patterns of Snail, E-cad and N-cad in human lung tissues were detected by immunohistochemistry, from 59 untreated NSCLC patients in Affiliated Cancer Hospital of Xinjiang Medical University from January 2014 to December 2015 for whom clinical data were available, with adjacent tissues and 31 benign lesions as control. The expression patterns of Snail, E-cad, N-cad and clinicopathological factors were analyzed. Results The positive rate of Snail and N-cad in NSCLC was significantly higher than those in the control tissues [81.4% (48/59) vs. 37.3% (22/59) vs. 12.9% (4/31), χ2 = 9.782, P < 0.05; 76.3% (45/59) vs. 33.9% (20/59) vs. 12.9% (4/31), χ2 = 7.445, P < 0.05]. The positive rate of E-cad in NSCLC was significantly lower than those in the control tissues [20.3% (12/59) vs. 55.9% (33/59) vs. 93.5% (29/31), χ2 = 45.107, P < 0.01]. The expressions of Snail and E-cad were related to lymph node metastasis and TNM stage [snail: 97.5% (39/40) vs. 47.4% (9/19), χ2 = 7.734, P < 0.05; 12.5% (1/8) vs. 81.0% (17/21) vs. 100.0% (30/30), χ2 = 7.723, P < 0.05; E-cad: 95.0% (38/40) vs. 36.8% (7/19), χ2 = 7.190, P < 0.05; 100.0% (8/8) vs. 19.0% (4/21) vs. 0 (0/30), χ2 = 12.311, P < 0.01]. The expression of N-cad was related to lymph node metastasis, histological grade and TNM stage [97.5% (39/40) vs. 47.4% (9/19), χ2 = 11.231, P < 0.01; 28.6% (2/7) vs. 63.6% (14/22) vs. 96.7% (29/30), χ2 = 9.564, P < 0.05; 12.5% (1/8) vs. 85.7% (18/21) vs. 86.7% (26/30), χ2 = 11.664, P < 0.01]. The positive correlation was found between Snail and N-cad (r = 0.373, P < 0.01), the negative correlation was found between the expression of Snail and E-cad, N-cad and E-cad (r = -0.667, P = 0.00; r = -0.297, P = 0.01). Conclusion Snail, E-cad and N-cad are involved in the development, progression and metastasis of NSCLC, and combined detection can predict tumor invasion, metastasis and prognosis. Key words: Carcinoma, non-small-cell lung; Snail; E-cadherin; N-cadherin

Role of MAPK signaling pathway in epithelial-mesenchymal transition of type II alveolar epithelial cells induced by Paraquat

Objective: To investigate the roles of p38 mitogen-activated protein kinases (p38 MAPK) , extracellular regulated protein kinases (ERK) and c-Jun N-tenninal kinases (JNK) of MAPK signaling pathway in Paraquat-induced epithelial to mesenchymal transition (EMT) of type II alveolarepithelial cells. Methods: RLE-6NT cells were incubated with different concentrations of PQ (0, 25, 50, 100μmol/L) for 6, 12 and 24 h. Cell morphology alteration was observed under phase-contrast microscopy. Cell viability was determined using an MTT assay. Cell migration ability was detected using scratch wound assay. Protein expression of P-p38 MAP, P-Erk1/2, P-JNK, E-cad, ZO-1, Vimentin and а-SMA were detected by western blot. The level of genes related to fibrosis (COL-I, COL-III, FN and FSP-1) were analyzed via quantitative real-time RT-PCR. Results: Cell morphology started to undergo EMT changes with a phenotype characteristic of mesenchymal cells, including an elongated shape and a lack of tight cell-cell adhesions induced by 100μmol/L PQ treatment in a time-dependent manner. MTT showed that cell viability decreased with increasing PQ concentration (50、100、200、300 μmol/L PQ treatment for 24 h) and increasing treatment time (200 μmol/L PQ treatment for 6, 12, 24, 36, 48 h) . Compared to control group, the expressions of the epithelial phenotype marker E-cad and ZO-1 significantly decreased with PQ treatment (50, 100μmol/L) in a time-dependent manner (P<0.05) . Additionally, the level of the mesenchymal marker (a-SMA, vimentin) dramatically increased with PQ treatment in the same concentration-and time-dependent manner (P<0.05) . Cell migration ability was markedly increased after 24 h of 100 μmol/L PQ treatment compared to control (P<0.05) . The phosphorylated forms of p38 MAPK, Erk1/2, and JNK were increased at 24 h after stimulation with PQ (P<0.05) . This PQ induced (100 μmol/L) phosphorylation was markedly attenuated in the presence of the p38 MAPK, ERK and JNK inhibitors (SB-203580, SP-600125 and PD98059) respectively. Furthermore, RT-PCR showed that PQ significantly induced the upregulation expression of COL I and III mRNA, Fn, and FSP-1 mRNA (P<0.05) . Conclusion: PQ-induced pulmonary fibrosis occurs via EMT, which is mediated by the MAPK pathway.